Multi-Curie Production of Gallium-68 on a Biomedical Cyclotron and Automated Radiolabelling of PSMA-11 and DOTATATE

Thisgaard, Helge; Kumlin, Joel; Langkjær, Niels; Chua, Jansen; Hook, Brian; Jensen, Mikael; Kassaian, Amir; Zeisler, Stefan; Borjian, Sogol; Cross, Michael; Schaffer, Paul; Dam, Johan Hygum

doi:10.21203/rs.3.rs-70698/v1

Cited by 4 publications

(9 citation statements)

References 5 publications

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“…However, as in all [ 68 Ga]-Ga-labeled radiotracers, the capacity of the examination of [ 68 Ga]-Ga-PSMA-11 is limited by its short half-life of only 68min, requiring in most cases in-house production and a sufficient generator supply. However, cyclotron-based production methods have recently been developed [10]. The output of more than 100 GBq could possibly allow satellite distribution of [ 68 Ga]-Ga-labeled tracers equivalently to [ 18 F]-F-tracers.…”

Section: Introductionmentioning

confidence: 99%

Intraindividual comparison of [68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 in prostate cancer patients: a retrospective single-center analysis

et al. 2021

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Background The analysis aimed to compare the radiotracers [68Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 intraindividually in terms of malignant lesions, mi(molecular-imaging)TNM staging and presumable unspecific lesions retrospectively as used in routine clinical practice. Methods A retrospective analysis of 46 prostate cancer patients (median age: 71 years) who underwent consecutive [68Ga]-Ga-PSMA-11- and [18F]-F-PSMA-1007-PET/CT or PET/MRI within a mean of 12 ± 8.0 days was performed. MiTNM staging was performed in both studies by two nuclear medicine physicians who were blinded to the results of the other tracer. After intradisciplinary and interdisciplinary consensus with two radiologists was reached, differences in both malignant and presumable nonspecific tracer accumulation were analyzed. Results Differences in terms of miTNM stages in both studies occurred in nine of the 46 patients (19.6%). The miT stages differed in five patients (10.9%), the miN stages differed in three patients (6.5%), and different miM stages occurred only in one patient who was upstaged in [18F]-F-PSMA-1007 PET. Concordant miTNM stages were obtained in 37 patients (80.4%). There was no significant difference between [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11 in the SUVmax locally (31.5 vs. 32.7; p = 0.658), in lymph node metastases (28.9 vs. 24.9; p = 0.30) or in bone metastases (22.9 vs. 27.6; p = 0.286). In [18F]-F-PSMA-1007 PET, more patients featured presumable unspecific uptake in the lymph nodes (52.2% vs. 28.3%; p: < 0.001), bones (71.7% vs. 23.9%; p < 0.001) and ganglia (71.7% vs. 43.5%; p < 0.001). Probable unspecific, exclusively [18F]-F-PSMA-1007-positive lesions mainly occurred in the ribs (58.7%), axillary lymph nodes (39.1%) and cervical ganglia (28.3%). Conclusion In terms of miTNM staging, both tracers appeared widely exchangeable, as no tracer relevantly outperformed the other. The differences between the two tracers were far more common in presumable unspecific lesions than in malignant spots. A routinely performed two-tracer study could not be shown to be superior. Since it seems at least challenging for most nuclear medicine departments to provide both [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11, it appears reasonable to choose the PSMA radiotracer depending on local availability with attention to the greater occurrence of nonspecific bone findings with [18F]-F-PSMA-1007.

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Section: Introductionmentioning

confidence: 99%

Intraindividual comparison of [68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 in prostate cancer patients: a retrospective single-center analysis

et al. 2021

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“…The target put in target chamber with 300 mg mass (11). The foil as a cover using materials such as havar, aluminum, niobium and titanium with a thickness between 25 to 50 µm (24).…”

Section: Experimental Section Target Materialsmentioning

confidence: 99%

“…The total flux of gamma-ray obtained 1.55x10 11 source.s -1 has 4.10x10 10 source.s -1 with energy 511 keV which was identic characteristic with photon from positron and electron annihilation reaction. 16 8.63x10 10 Germanium-71 9.59x10 16 6.73x10 10 Gallium-68 1.10x10 12 1.88x10 8 Germanium-68 6.36x10 15 1.88x10 8 Gallium-72 2.92x10 11 3.98x10 6…”

Section: Irradiation Processmentioning

confidence: 99%

“…The radioactivity generated during the irradiation process of producing a dose that was shown in the figure 8 below: The production 68 Ga process from irradiation of 68 Zn resulted high radionuclide purity with 1.5-2 time of half life irradiation times (33). Activity data obtained at intervals of 10 -240 minutes of irradiation can be seen in the graph below: 11 1.42x10 15 Germanium-70 4.41x10 7 8.07x10 10 Germanium-67 3.23x10 7 1.31x10 13 Germanium-66 2.10x10 7 1.03x10 12 Zinc-69 5.14x10 6 2.50x10 10…”

Section: Graph Of High Activity Process For (A) Activated Atom and (B...mentioning

confidence: 99%

“…The production of 68 Ga that was used Zinc-68 enriched as a target can obtain high radioactivity which was can generate smoother imagine on diagnostic purpose. (11), but the extraction from another radionuclides impurity hard to be done (12)…”

Section: Introductionmentioning

confidence: 99%

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Computation Study of Radioisotopes Gallium-68 (68Ga) Production using Long-lived & High Activity methods

Rattyananda

Martoprawiro

Arifah

et al. 2022

JSTNI

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Radioisotopes used for gamma-ray-based diagnostics have the main problem that imaging resolution quality.Gallium-68 is a positron (β+) emitting radioisotope that has better imaging resolution than gamma-based radioisotopes. Gallium-68 (68Ga) can be produced by irradiating natural gallium or zinc-68 enriched as a target with protons in an accelerator facility. Indonesia has planned to build a cyclotron type accelerator that operates in 13 MeV proton energy and 50 µA proton beam who has initials named DECY-13. Before it was commissioned for radioisotopes production purpose that was must conduct a preliminary study to determine 68Ga optimum irradiation time and properties, one of which was the monte carlo computation method using PHITS v3.24 software. Simulations were begun by irradiating proton with natural gallium target for 25 days with 2 days cooling and zinc-68 enriched for 120 minutes with cooling 10 minutes. The results at EOB of the long-lived process using the natGa target obtained total radioactivity of 189.42 MBq (5.12 mCi). The total radioactivity result of high activity process which used 68Zn enriched as a target was 268.6 GBq (7.259 Ci). the radioactivity was compared with another accelerator, that the long-lived process was too small and uneconomical to done, but the high activity process was feasible to produce. The results of this research expected will be considered as a feasibility study for the 68Ga production process in Indonesia in the future.

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⁶⁸Ga-DOTATATE Prepared from Cyclotron-Produced⁶⁸Ga: An Integrated Solution from Cyclotron Vault to Safety Assessment and Diagnostic Efficacy in Neuroendocrine Cancer Patients

Tremblay

Benesty²,

Aı̈t-Mohand³

et al. 2022

J Nucl Med

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Cyclotron production of gallium-68 ( 68 Ga) is a promising approach to supply 68 Ga radiopharmaceuticals. To validate this capability, an integrated solution for a robust synthesis of 68 Ga-DOTATATE prepared from cyclotron produced 68 Ga (further on referred to as cyclotron produced 68 Ga-DOTATATE) was achieved. A retrospective comparison analysis was performed in patients who underwent PET/CT imaging after injection of DOTATATE labeled with 68 Ga produced by cyclotron or eluted from a generator to demonstrate the clinical safety and diagnostic efficacy of the radiopharmaceutical for a routine standard-of-care diagnostic tool in clinic. Methods: An enriched zinc-68 pressed target was irradiated by cyclotron with a proton beam set at 12.7 MeV for 100 min. The fully automated process utilizes an in-vault dissolution system where a liquid distribution system transfers the dissolved target to a dedicated hotcell for the purification of 68 GaCl3 and radiolabeling of DOTATATE using a cassette-based automated module. Quality control tests were performed on the resulting tracer solution. The internal radiation dose for 68 Ga-DOTATATE was calculated based on extrapolation from rat biodistribution experiments. A retrospective comparison analysis was performed in patients who underwent PET/CT imaging after injection of DOTATATE labeled with 68 Ga produced by cyclotron or eluted from a generator. Results: The synthesis of 68 Ga-DOTATATE (20.7 ± 1.3 GBq) with high apparent molar activity (518 ± 32 GBq/µmole at end of synthesis (EOS)) was completed in 65 min and the radiopharmaceutical met the requirements specified in the European Pharmacopoeia monograph on Gallium ( 68 Ga) chloride (accelerator produced) solution for radiolabeling. 68 Ga-DOTATATE was stable for at least 5 h after formulation. The dosimetry calculated with OLINDA for 68 Ga-DOTATATE from cyclotron produced 68 Ga and generator eluted 68 Ga was roughly equivalent. The SUVmean or SUVmax of tumoral lesions with cyclotron produced 68 Ga-DOTATATE was equivalent to that with generator-eluted 68 Ga. Among physiological uptakes, a significant difference was found in kidneys, spleen and stomach wall, with lower values in cyclotron produced 68 Ga-DOTATATE in all cases. Conclusion: Integrated cyclotron production achieves reliable high yields of clinical-grade 68 Ga-DOTATATE. The clinical safety, and imaging efficacy of cyclotron produced 68 Ga-DOTATATE in humans provide supporting evidence for its use in routine clinical practice.

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Multi-Curie Production of Gallium-68 on a Biomedical Cyclotron and Automated Radiolabelling of PSMA-11 and DOTATATE

Cited by 4 publications

References 5 publications

Intraindividual comparison of [68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 in prostate cancer patients: a retrospective single-center analysis

Intraindividual comparison of [68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 in prostate cancer patients: a retrospective single-center analysis

Computation Study of Radioisotopes Gallium-68 (68Ga) Production using Long-lived & High Activity methods

⁶⁸Ga-DOTATATE Prepared from Cyclotron-Produced⁶⁸Ga: An Integrated Solution from Cyclotron Vault to Safety Assessment and Diagnostic Efficacy in Neuroendocrine Cancer Patients

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Multi-Curie Production of Gallium-68 on a Biomedical Cyclotron and Automated Radiolabelling of PSMA-11 and DOTATATE

Cited by 4 publications

References 5 publications

Intraindividual comparison of [68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 in prostate cancer patients: a retrospective single-center analysis

Intraindividual comparison of [68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 in prostate cancer patients: a retrospective single-center analysis

Computation Study of Radioisotopes Gallium-68 (68Ga) Production using Long-lived & High Activity methods

68Ga-DOTATATE Prepared from Cyclotron-Produced68Ga: An Integrated Solution from Cyclotron Vault to Safety Assessment and Diagnostic Efficacy in Neuroendocrine Cancer Patients

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Product

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⁶⁸Ga-DOTATATE Prepared from Cyclotron-Produced⁶⁸Ga: An Integrated Solution from Cyclotron Vault to Safety Assessment and Diagnostic Efficacy in Neuroendocrine Cancer Patients